Epistasis Is a Major Determinant of the Additive Genetic Variance in Mimulus guttatus

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author’s publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.The influence of genetic interactions (epistasis) on the genetic variance of quantitative traits is a major unresolved problem relevant to medical, agricultural, and evolutionary genetics. The additive genetic component is typically a high proportion of the total genetic variance in quantitative traits, despite that underlying genes must interact to determine phenotype. This study estimates direct and interaction effects for 11 pairs of Quantitative Trait Loci (QTLs) affecting floral traits within a single population of Mimulus guttatus. With estimates of all 9 genotypes for each QTL pair, we are able to map from QTL effects to variance components as a function of population allele frequencies, and thus predict changes in variance components as allele frequencies change. This mapping requires an analytical framework that properly accounts for bias introduced by estimation errors. We find that even with abundant interactions between QTLs, most of the genetic variance is likely to be additive. However, the strong dependency of allelic average effects on genetic background implies that epistasis is a major determinant of the additive genetic variance, and thus, the population’s ability to respond to selection.This work was supported by the National Institute of Health (Grant #: NIH 69314). http://www.nih.gov/ The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Skin disease and non-syndromic hearing loss-linked Cx30 mutations exhibit several distinct cellular pathologies

Connexin 30 (Cx30), a member of the large gap junction protein family, plays a role in the homeostasis of the epidermis and inner ear through gap junctional intercellular communication (GJIC). Here, we investigated the underlying mechanisms of four autosomal dominant Cx30 gene mutations linked to hearing loss and/or various skin diseases. First, the T5M mutant linked to non-syndromic hearing loss formed functional gap junction channels and hemichannels, similar to wild type Cx30. The loss-of-function V37E mutant associated with Clouston syndrome or keratitis-ichthyosis-deafness syndrome was retained in the endoplasmic reticulum and significantly induced apoptosis. The G59R mutant linked to Vohwinkel and Bart-Pumphrey syndromes was retained primarily in the Golgi apparatus and exhibited loss of gap junction channel and hemichannel function, but did not cause cell death. Lastly, the A88V mutant related to Clouston syndrome also significantly induced apoptosis, although through an endoplasmic reticulum-independent mechanism. Collectively, we discovered that four unique Cx30 mutants may cause disease through different mechanisms that also likely include their selective transdominant effects on co-expressed connexins, highlighting the overall complexity of connexin-linked diseases and the importance of GJIC in disease prevention

Survey of vector-borne agents in feral cats and first report of Babesia gibsoni in cats on St Kitts, West Indies

Background: As there is little data on vector-borne diseases of cats in the Caribbean region and even around the world, we tested feral cats from St Kitts by PCR to detect infections with Babesia, Ehrlichia and spotted fever group Rickettsia (SFGR) and surveyed them for antibodies to Rickettsia rickettsii and Ehrlichia canis. Results: Whole blood was collected from apparently healthy feral cats during spay/ neuter campaigns on St Kitts in 2011 (N = 68) and 2014 (N = 52). Sera from the 52 cats from 2014 were used to detect antibodies to Ehrlichia canis and Rickettsia rickettsii using indirect fluorescent antibody tests and DNA extracted from whole blood of a total of 119 cats (68 from 2011, and 51 from 2014) was used for PCRs for Babesia, Ehrlichia and Rickettsia. We could not amplify DNA of SFG Rickettsia in any of the samples but found DNA of E. canis in 5% (6/119), Babesia vogeli in 13% (15/119), Babesia gibsoni in 4% (5/119), mixed infections with B. gibsoni and B. vogeli in 3% (3/119), and a poorly characterized Babesia sp. in 1% (1/119). Overall, 10% of the 52 cats we tested by IFA for E. canis were positive while 42% we tested by indirect fluorescent antibody (IFA) for R. rickettsii antigens were positive. Conclusions: Our study provides the first evidence that cats can be infected with B. gibsoni and also indicates that cats in the Caribbean may be commonly exposed to other vector-borne agents including SFGR, E. canis and B. vogeli. Animal health workers should be alerted to the possibility of clinical infections in their patients while public health workers should be alerted to the possibility that zoonotic SFGR are likely circulating in the region

First Molecular Characterization of Bovine Leukemia Virus Infections in the Caribbean

Citation: Yang Y, Kelly PJ, Bai J, Zhang R, Wang C (2016) First Molecular Characterization of Bovine Leukemia Virus Infections in the Caribbean. PLoS ONE 11(12): e0168379. doi:10.1371/journal.pone.0168379Bovine leukemia virus (BLV) is a retrovirus that causes enzootic bovine leucosis. To investigate the presence and genetic variability of BLV in the Caribbean for the first time, we preformed fluorescence resonance energy transfer (FRET)-PCR for the pol of BLV on DNA from whole blood of cattle from Dominica, Montserrat, Nevis and St. Kitts. Standard PCRs with primers for the env were used for phylogenetic analysis of BLV in positive animals. We found FRET-PCR positive cattle (12.6%, 41/325) on Dominica (5.2%; 4/77) and St. Kitts (19.2%; 37/193) but not on Montserrat (0%, 0/12) or Nevis (0%, 0/43). Positive animals were cows on farms where animals were raised intensively. Phylogenetic analysis using the neighbor-joining (NJ) method on partial and full-length env sequences obtained for strains from Dominica (n = 2) and St. Kitts (n = 5) and those available in GenBank (n = 90) (genotypes 1–10) revealed the Caribbean strains belonged to genotype 1 (98–100% sequence homology). Ours is the first molecular characterization of BLV infections in the Caribbean and the first description of genotype 1 in the region

The Natural History and Clinical Syndromes of Degenerative Cervical Spondylosis

Cervical spondylosis is a broad term which describes the age related chronic disc degeneration, which can also affect the cervical vertebrae, the facet and other joints and their associated soft tissue supports. Evidence of spondylitic change is frequently found in many asymptomatic adults. Radiculopathy is a result of intervertebral foramina narrowing. Narrowing of the spinal canal can result in spinal cord compression, ultimately resulting in cervical spondylosis myelopathy. This review article examines the current literature in relation to the cervical spondylosis and describes the three clinical syndromes of axial neck pain, cervical radiculopathy and cervical myelopath

Predicting evolutionary change at the DNA level in a natural Mimulus population

Evolution by natural selection occurs when the frequencies of genetic variants change because individuals differ in Darwinian fitness components such as survival or reproductive success. Differential fitness has been demonstrated in field studies of many organisms, but it remains unclear how well we can quantitatively predict allele frequency changes from fitness measurements. Here, we characterize natural selection on millions of Single Nucleotide Polymorphisms (SNPs) across the genome of the annual plant Mimulus guttatus. We use fitness estimates to calibrate population genetic models that effectively predict allele frequency changes into the next generation. Hundreds of SNPs experienced “male selection” in 2013 with one allele at each SNP elevated in frequency among successful male gametes relative to the entire population of adults. In the following generation, allele frequencies at these SNPs consistently shifted in the predicted direction. A second year of study revealed that SNPs had effects on both viability and reproductive success with pervasive trade-offs between fitness components. SNPs favored by male selection were, on average, detrimental to survival. These trade-offs (antagonistic pleiotropy and temporal fluctuations in fitness) may be essential to the long-term maintenance of alleles. Despite the challenges of measuring selection in the wild, the strong correlation between predicted and observed allele frequency changes suggests that population genetic models have a much greater role to play in forward-time prediction of evolutionary change

A High-Resolution Genetic Map of Yellow Monkeyflower Identifies Chemical Defense QTLs and Recombination Rate Variation

Genotyping-by-sequencing methods have vastly improved the resolution and accuracy of genetic linkage maps by increasing both the number of marker loci as well as the number of individuals genotyped at these loci. Using restriction-associated DNA sequencing, we construct a dense linkage map for a panel of recombinant inbred lines derived from a cross between divergent ecotypes of Mimulus guttatus. We used this map to estimate recombination rate across the genome and to identify quantitative trait loci for the production of several secondary compounds (PPGs) of the phenylpropanoid pathway implicated in defense against herbivores. Levels of different PPGs are correlated across recombinant inbred lines suggesting joint regulation of the phenylpropanoid pathway. However, the three quantitative trait loci identified in this study each act on a distinct PPG. Finally, we map three putative genomic inversions differentiating the two parental populations, including a previously characterized inversion that contributes to life-history differences between the annual/perennial ecotypes.We thank M. Montenero and K. Keefover-Ring for assistance in phytochemistry sample preparation and HPLC troubleshooting, respectively. The KU EEB Genetics group provided valuable comments on the manuscript. We also thank Emma Huang and two anonymous reviewers for their comments. Funding for this research was provided by National Science Foundation grants DEB-0841609 (to RLL) and IOS-0951254 (to J.K.K.), by NIH grant GM073990 (to J.K.K.), and funding from the University of Kansas Botany Endowment Funds (to P.J.M.)

Prevalence and risk factors for diabetes mellitus among tuberculosis patients in Moshi Municipal Council, Kilimanjaro Tanzania

Background: Diabetes Mellitus (DM) is a worldwide public health problem and its prevalence has been rising rapidly in low and middle income countries (LMICs) including Tanzania. According to WHO report 2015, DM is ranked number six as a leading cause of death  worldwide. Strong evidence suggests that DM may be associated with Tuberculosis (TB) and could affect TB treatment outcomes. Tanzania is among the 22 countries that have a high burden of TB and currently facing increased epidemic of DM. The increasing diabetes  prevalence may be a threat to TB control and counteract strategies to end TB by 2030 as proposed by WHO.Objective: To determine proportion of TB patients who are co-infected with DM in Moshi municipal council, Kilimanjaro Tanzania.Methodology: This study was a hospital based cross-sectional study conducted in April to July 2018 at 4 health facilities; Mawenzi Regional Referral hospital, St. Joseph District Designated hospital, Pasua Health center and Majengo Health centre in Moshi municipal. The study included adults aged 18 years and above attending either of the 4 health facilities for TB care. The study included newly diagnosed and those who were on TB treatment. Interviews were conducted followed by blood glucose testing. Data was entered and analysed using SPSSResults: A total of 153 TB patients were enrolled, their mean age was 42.5 (±14.75) years and 46 (30.1%) were females. The prevalence of DM among TB patients in this study was 9.2%. Factors associated with TB-DM comorbidity were: age (OR 4.43, 95% CI: 1.18-16.55), HIV status (OR 3.88, 95% CI: 1.06-14.11), and family history of DM (OR 6.50, 95% CI 0.67-25.56).Conclusion: One in ten patients with TB had confirmed DM. There is a need for future studies to assess if DM influences TB treatment and outcomes in this setting